crossing96/oncoscreening huggingface dataset:
Low dose geldanamycin inhibits hepatocyte growth factor and hypoxia-stimulated invasion of cancer cells.	Hepatocyte growth factor (HGF) receptor Met and hypoxia-inducible factor-1 (HIF-1) signaling pathways are commonly activated in aggressive tumors and promote progression. Since both Met and HIF-1alpha proteins are heat shock protein (Hsp) 90 clients, Hsp90 inhibitors might be expected to positively impact tumor progression. Here, we systematically evaluated the inhibitory effects of the prototypical Hsp90 inhibitor geldanamycin (GA) on cellular processes involved in invasion and angiogenesis in T24 bladder cancer cells stimulated with HGF and chemical hypoxia. First, we demonstrated the positive feedback loop between Met and HIF-1 pathways, which serves to sustain and amplifies their signaling in T24 cells. GA downregulated Met by inhibiting new protein maturation, thereby dampening HGF signaling. HGF and chemical hypoxia with CoCl2 cooperatively promoted in vitro invasion and vascular endothelial growth factor (VEGF) secretion, while CoCl2 but not HGF activated urokinase-type plasminogen activator and matrix metalloproteinase 2, both of which promote invasion and angiogenesis. Low dose GA (100 nmol/L) inhibited these processes by suppressing both HGF and HIF-1 pathways. Notably, brief GA pretreatment inhibited in vitro invasion and VEGF secretion induced by HGF as effectively as did continuous treatment. Moreover, we found that GA inhibited activation of focal adhesion kinase, focal adhesion assembly, and actin reorganization induced by HGF and integrin engagement by extracellular matrix. Thus, GA widely suppresses extrinsic stimuli-induced signaling that contribute to tumor invasion and angiogenesis in this bladder carcinoma model, suggesting the utility of Hsp90 inhibitors in preventing tumor progression and metastasis.	bladder
Bladder cancer associated glycoprotein signatures revealed by urinary proteomic profiling.	Current methods in the noninvasive detection and surveillance of bladder cancer via urine analysis include voided urine cytology (VUC) and some diagnostic urinary protein biomarkers; however, due to the poor sensitivity of VUC and high false-positive rates of currently available protein assays, detection of bladder cancer via urinalysis remains a challenge. In the study presented here, a rapid, high-sensitivity technique was developed to profile the N-linked glycoprotein component in naturally micturated human urine specimens. Concanavalin A (Con A) affinity chromatography coupled to nanoflow liquid chromatography was utilized to separate the complex peptide mixture prior to a linear ion trap MS analysis. Of 186 proteins identified with high confidence by multiple analyses, 40% were secreted proteins, 18% membrane proteins, and 14% extracellular proteins. In this study, the presence of several proteins appeared to be associated with the presence of bladder cancer, including alpha-1B-glycoprotein that was detected in all tumor-bearing patient samples but in none of the samples obtained from non-tumor-bearing individuals. The combination of Con A affinity chromatography and nano-LC/MS/MS provides an initial investigation of N-glycoproteins in complex biological samples and facilitates the identification of potential biomarkers of bladder cancer in noninvasively obtained human urine.	bladder
Adverse events of MVAC chemotherapy in patients with advanced urothelial cancer of the bladder.	There have only been a few reports about adverse events of methotrexate, vinblastine, adriamycin and cisplatin (MVAC) chemotherapy under supportive care with granulocyte stimulating factor (G-CSF) and 5-hydroxytryptamine 3 receptor (5-HT3R) antagonists. The purpose of this study was to retrospectively review the adverse events of the chemotherapy. We analyzed 59 patients with advanced bladder cancer who received MVAC chemotherapy at Sapporo Medical University hospital from January 1992 to September 2004. The adverse events were evaluated according to the Common Terminology Criteria for Adverse Events version 3.0 (Japanese edition). Thirty-one of the 59 patients (52.6%) received MVAC in the neoadjuvant setting. Two courses of chemotherapy were most frequently used in the neoadjuvant and adjuvant settings, and treatment of metastatic or recurrent lesions. More than 90% of patients experienced hematological adverse events such as some grade of leukocytopenia and neutropenia in each course of the chemotherapy. Grade 3 or 4 neutropenia was seen in 60-75% of patients. Grade 3 or 4 leukopenia and/or neutropenia in the first course of the chemotherapy was associated with patients with impaired renal function (60 mL/min< or = creatinine clearance <80 mL/min). Febrile neutropenia was found in 6 patients (5.0%), including one who died of subsequent septic shock and adult respiratory distress syndrome. Nausea was seen in 70-80% of patients. MVAC chemotherapy for advanced bladder cancer was performed with tolerable adverse events. The current results provide relevant information mainly for those who need 2 courses of chemotherapy in the neoadjuvant or adjuvant setting.	bladder
Mcm2 predicts recurrence hazard in stage Ta/T1 bladder cancer more accurately than CK20, Ki67 and histological grade.	Stage Ta/T1 urothelial carcinoma of the bladder (Ta/T1 BC) has a marked tendency to recur. Besides histopathology, markers such as CK20 expression and proliferation index (Ki67) have been shown to predict its clinical course. The replication-licensing factor minichromosome maintenance protein 2 (Mcm2) is a marker of proliferative potential shown to be a promising prognostic marker in various malignancies. The aim of the present study was to evaluate the prognostic value of Mcm2 in comparison to stage, grade, CK20 and Ki67. Initial sporadic Ta/T1 BC (n=71) were evaluated for their expression of CK20, Ki67 and Mcm2 by immunohistochemistry and tissue microarray technology. Prognostic power was analysed by univariate and multivariate Cox regression model for tumour recurrence rate. Median follow-up period was 39 months. A total of 35% patients experienced recurrence. While CK20 was not predictive, grade, Ki67 and Mcm2 were significantly related to recurrence rate in univariate Cox regression model. Only grade (HR 2.37; 95% CI 1.24-4.51; P=0.009) and Mcm2 expression with a cutoff > or = 40% (HR 5.81; 95% CI 2.41-14.00; P<0.001) were independent predictors of recurrence rate in multivariate Cox regression analysis. In addition to grade, expression of Mcm2 is an independent predictor of recurrence in Ta/T1 BC.	bladder
[Systemic oncological treatment of bladder cancer].	M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) and Cisplatin/Gemzar are potent therapies in the treatment of advanced bladder cancer. C/G provides similar efficacy in terms of overall survival compared with M-VAC, but does so with a superior safety profile. Therefore C/G is widely accepted as standard of care in locally advanced and metastatic bladder cancer. Despite potentially curative surgery almost half of the patients with muscle-invasive bladder cancer will have recurrence of disease. Based on a recent meta-analysis with data from 3005 patients, and 2 randomised studies, neoadjuvant cisplatin-containing therapy has shown to improve overall survival. Thus, the use of neoadjuvant systemic treatment should be considered state-of-the-art. The question whether adjuvant treatment will improve the outcome is still not sufficiently answered.	bladder
[Bladder cancer and occupation: a descriptive analysis in Haute Normandie in 2003].	OBJECTIVE: Haute Normandie is characterized by the presence of a large number of industries likely to have exposed their employees to a risk of bladder cancer. The objective of the study performed by Assurance Maladie (national health insurance) and Réseau d'Onco-Urologie de Haute Normandie (ROUHN) (Haute Normandie Urological Oncology Network) was to describe the epidemiological characteristics of bladder cancers and to estimate the proportion of potentially work-related cancers. MATERIAL: A questionnaire elaborated for the study and comprising demographic, clinical, environmental and occupational data was completed for all patients in whom exemption of co-payment for bladder cancer was requested in 2003. RESULTS: The population comprised 258 patients with a mean age of 70.4 years. The sex-ratio was five males for one female. Tumours were diagnosed at an early stage: 73.9% of superficial tumours and 26.1% of invasive lesions. 72.1% of subjects were current smokers or ex-smokers (mean of 32 packet-years). Among the 41% of occupationally exposed subjects, 47.2% were mainly exposed to polycyclic aromatic hydrocarbons, 27.4% to diesel smoke and 17.9% to aromatic amines. Based on a multidisciplinary consultation, 14.7% of patients (n = 38) were considered to be eligible for an occupational disease declaration. CONCLUSION: This study demonstrated that the incidence of occupational bladder cancers is underestimated. The urologist plays an essential role in the recognition of all risk factors of bladder cancer, as a history of smoking does not exclude the possibility of an occupational cause.	bladder
Significance of target cell infection and natural killer cells in the anti-tumor effects of bacillus Calmette-Guerin in murine bladder cancer.	Although intravesical instillation of bacillus Calmette-Guerin (BCG) is a clinically well-recognized therapy for bladder carcinoma in situ and recurrence prophylaxis, these mechanisms have not been fully understood. We studied the effects of BCG infection (Connaught strain) on target cancer cells and host immune systems in murine bladder cancer. The bladder cancer cell line, MB49, was used in C57/BL6 mice in vivo and in vitro. In vitro cytotoxicities against the cancer cell line were measured by 24-h 51Cr release assay. For effector cells, spleen mononuclear cells were obtained from mice injected intraperitoneally with BCG or BCG-infected irradiated MB49 cells. Although BCG infection of cancer cells did not affect the proliferation speed in vitro, the mice injected subcutaneously with BCG-infected MB49 cells survived significantly longer than those given untreated cancer cells. The mice surviving without tumor growth after injection of BCG-infected cancer cells could not reject a second injection of intact MB49 cells. In vitro cytotoxicity was enhanced by BCG infection of target cancer cells, but not by immunizing the mice with BCG from which effector cells were obtained. Moreover, cytotoxicity disappeared by depleting natural killer (NK) cells from effector cells. Although in vitro cytotoxicity was increased by immunizing the mice with BCG-infected irradiated MB49 cells, survival did not improve in these mice. These results suggest that a major part of BCG's anti-tumor effects can be attributed to the elimination of BCG-infected cancer cells by NK cells.	bladder
Penalized item response theory models: application to epigenetic alterations in bladder cancer.	Increasingly used in health-related applications, latent variable models provide an appealing framework for handling high-dimensional exposure and response data. Item response theory (IRT) models, which have gained widespread popularity, were originally developed for use in the context of educational testing, where extremely large sample sizes permitted the estimation of a moderate-to-large number of parameters. In the context of public health applications, smaller sample sizes preclude large parameter spaces. Therefore, we propose a penalized likelihood approach to reduce mean square error and improve numerical stability. We present a continuous family of models, indexed by a tuning parameter, that range between the Rasch model and the IRT model. The tuning parameter is selected by cross validation or approximations such as Akaike Information Criterion. While our approach can be placed easily in a Bayesian context, we find that our frequentist approach is more computationally efficient. We demonstrate our methodology on a study of methylation silencing of gene expression in bladder tumors. We obtain similar results using both frequentist and Bayesian approaches, although the frequentist approach is less computationally demanding. In particular, we find high correlation of methylation silencing among 16 loci in bladder tumors, that methylation is associated with smoking and also with patient survival.	bladder
Granular cell tumour of the urinary bladder: a case report and review of the literature.	Granular cell tumor of the urinary bladder is an exceedingly rare disease, with only 10 cases reported so far in literature. We report a case of granular cell neoplasm of the bladder incidentally found in a 44-year-old woman during an abdominal ultrasound examination for evaluation of stress urinary incontinence. The patient underwent a transurethral resection of the mass and histological examination revealed the presence of a granular cell tumor. Immunohistochemical staining for neuron-specific enolase and S100 protein was positive. At a 6-month follow-up the patient is free of bladder recurrence.	bladder
Effect of bladder carcinoma location on detection rates by ultrasonography and computed tomography.	OBJECTIVES: To evaluate the effect of the location of bladder carcinoma on detection rates by ultrasonography (US) and computed tomography (CT). METHODS: The study included 85 patients with bladder cancer who were examined by US and CT before cystoscopy. The bladder wall was divided into 13 separate regions, and the tumor detection rates by US and CT were calculated for each location and lesion diameter with regard to the cystoscopy findings. RESULTS: A total of 214 bladder tumors were detected at cystoscopy. The lowest detection rate for US was noted for the anteroinferior region (47%) of the bladder. The lowest detection rate for CT was also noted for the same region (55.5%). The detection rate of all anterior wall tumors by US and CT was 48.27% and 62.5%, respectively. The detection rate by CT was 100% for tumors greater than 5 mm in diameter. The greatest detection rates by both of the imaging modalities were for the bilateral side walls of the bladder. CONCLUSIONS: The results of this study suggest that bladder tumor location highly affects the detection rates by US and CT. The lowest detection rates by both modalities were noted for anterior wall tumors. Because of the lower detection rate of tumors located in the anterior wall of bladder and those smaller than 5 mm, we recommend cystoscopy whenever a bladder tumor is suspected.	bladder
Volume, process of care, and operative mortality for cystectomy for bladder cancer.	OBJECTIVES: High-volume hospitals have lower mortality rates for a wide range of surgical procedures, including cystectomy for bladder cancer. However, the processes of care that mediate this effect are unknown. We sought to identify the processes that underlie the volume-outcome relationship for cystectomy. METHODS: Within the Surveillance, Epidemiology, and End Results (SEER)-Medicare data set, we used International Classification of Diseases (ICD)-9 procedure codes to identify 4465 patients who underwent cystectomy for bladder cancer between 1992 and 1999. The preoperative and perioperative processes of care were abstracted from the inpatient, outpatient, and physician files using the procedure and diagnosis codes available through 2002. Logistic models were used to assess the relationship between the process and hospital volume, adjusting for differences in patient characteristics. RESULTS: Substantial variation was found in the use of specific processes of care across the hospital volume strata. High-volume hospitals had greater rates of preoperative cardiac testing (odds ratio [OR] 1.57, 95% confidence interval [CI] 1.24 to 1.98), intraoperative arterial monitoring (OR 3.73, 95% CI 3.11 to 4.46), and the use of a continent diversion (OR 4.01, 95% CI 3.03 to 5.30), among many others. Patients treated at low-volume hospitals were 48% more likely to die in the postoperative period (4.9% versus 3.5%, adjusted OR 1.48, 95% CI 1.03 to 2.13). Differences in the use of processes of care explained 23% of this volume-mortality effect. CONCLUSIONS: High-volume and low-volume hospitals differ with regard to many processes of care before, during, and after radical cystectomy. Although these practices have partly explained the volume-outcome relationships for cystectomy, the primary mechanisms underlying this effect remain unclear.	bladder
18F-FDG PET/CT delayed images after diuretic for restaging invasive bladder cancer.	PET with (18)F-FDG has been considered of limited value for detection of bladder cancer because of the urinary excretion of the tracer. The purpose of this study was to investigate the role of PET/CT in the detection and restaging of bladder cancer using furosemide and oral hydration to remove the excreted (18)F-FDG from the bladder. METHODS: Seventeen patients with bladder cancer (11 without cystectomy, 6 with total cystectomy and urinary diversion) underwent (18)F-FDG PET/CT from head to the upper thighs 60 min after the intravenous injection of 370 MBq of (18)F-FDG. Additional pelvic images were acquired 1 h after the intravenous injection of furosemide and oral hydration. PET/CT findings were confirmed by MRI, cystoscopy, or biopsy. RESULTS: PET/CT was able to detect bladder lesions in 6 of 11 patients who had not undergone cystectomy. These images changed the PET/CT final reading in 7 patients: Recurrent bladder lesions were detected in 6 patients, pelvic lymph node metastases in 2 patients, and prostate metastasis in 1. This technique overcame the difficulties posed by the urinary excretion of (18)F-FDG. Hypermetabolic lesions could be easily detected by PET and precisely localized in the bladder wall, pelvic lymph nodes, or prostate by CT. Seven of 17 patients (41%) were upstaged only after delayed pelvic images. CONCLUSION: Detection of locally recurrent or residual bladder tumors can be dramatically improved using (18)F-FDG PET/CT with delayed images after a diuretic and oral hydration.	bladder
Combined endoscopic and laparoscopic en bloc resection of the urachus and the bladder dome in a rare case of urachal carcinoma.	Urachal carcinoma is a rare neoplasm treated with surgical resection. We report a case of adenocarcinoma of the urachus treated with a new surgical technique. In a 44-year-old man affected by urachal carcinoma we performed a combined endoscopic-laparoscopic surgical en bloc resection of the urachus and bladder dome. The procedure lasted 240 min, and no postoperative complications were recorded. The patient was discharged on fourth day and the catheter was removed on eighth day. Bladder capability resulted normal with no evident physical change. Multiple bladder biopsy and computed tomography scans at 6, 12 and 18 months proved negative.	bladder
Evaluation of direct versus non-refluxing technique and functional results in orthotopic Y-ileal neobladder after 12 years of follow up.	OBJECTIVES: We report on the long-term functional results of the orthotopic Y-ileal neobladder and compare the outcome of the antireflux technique for ureteral implantation versus direct anastomosis. PATIENTS AND METHODS: Between 1990 and 2002, 120 patients underwent cystoprostatectomy and orthotopic Y-shaped ileal neobladder for invasive bladder carcinoma. The direct Nesbit technique for ureteral reimplantation was applied in 58 patients (group 1) and in 62 patients the ureters were reimplanted using the Le Duc antirefluxing technique (group 2). The mean follow-up period was 72 months (range, 36-144 months). RESULTS: Of 62 patients who underwent the Le Duc technique, six (9.7%) had unilateral uretero-ileal anastomotic stricture and four (6.5%) had reflux. Of 58 patients who underwent direct anastomosis, six (10.3%) patients had unilateral reflux, four of them had dilated ureters preoperatively and no patient had uretero-ileal anastomotic stricture. The incidence of stricture formation in the Le Duc technique is significantly higher than direct anastomosis (P = 0.04). There was no significant difference in the overall incidence of reflux in both groups. However, the incidence of reflux in preoperatively dilated ureters was significantly higher in direct ureteral anastomosis than Le Duc technique (40% in group 1 vs 16.7% in group 2; P = 0.045). The incidence of stone formation, azotemia, pyelonephritis and bacteriuria was comparable in both groups. The urodynamic findings showed a mean increase in the neobladder capacity at 6 and 18 months after surgery by 340 and 560 mL, respectively. The mean of the maximum pressure was 22 +/- 10 cm H2O, 18 months after surgery. Daytime and nighttime continence was good or satisfactory in 93.3% and 85.5% of the patients, respectively, after 3 years of follow-up. CONCLUSIONS: The functional and voiding results of a Y-shaped neobladder pouch using 40 cm of ileum are similar to the more sophisticated larger pouches. Direct uretero-ileal anastomosis in orthotopic bladder replacement is more reasonable than the Le Duc antireflux technique in non-dilated ureters. The benefit of the antireflux technique has been overestimated despite of the frequency of stricture formation.	bladder
Radiochemotherapy with cisplatin and 5-fluorouracil after transurethral surgery in patients with bladder cancer.	PURPOSE: To give an update on the long-term outcome of an intensified protocol of combined radiochemotherapy (RCT) with 5-fluorouracil (5-FU) and cisplatin after initial transurethral resection of bladder tumor (TURBT) with selective organ preservation in bladder cancer. METHODS AND MATERIALS: One hundred twelve patients with muscle-invading or high-risk T1 (G3, associated Tis, multifocality, diameter >5 cm) bladder cancer were enrolled in a protocol of TURBT followed by concurrent cisplatin (20 mg/m(2)/day as 30-min infusion) and 5-FU (600 mg/m(2)/day as 120-h continuous infusion), administered on Days 1-5 and 29-33 of radiotherapy. Response to treatment was evaluated by restaging TURBT 4-6 weeks after RCT. In case of invasive residual tumor or recurrence, salvage cystectomy was recommended. RESULTS: Ninety-nine patients (88.4%) had no detectable tumor at restaging TURBT; 71 patients (72%) have been continuously free from local recurrence or distant metastasis. Superficial relapse occurred in 13 patients and muscle-invasive recurrence in 11 patients. Overall and cause-specific survival rates for all patients were 74% and 82% at 5 years, respectively. Of all surviving patients, 82% maintained their own bladder, 79% of whom were delighted or pleased with their urinary condition. Hematologic Grade 3/4 toxicity occurred in 23%/6% and Grade 3 diarrhea in 21% of patients. One patient required salvage cystectomy due to a shrinking bladder. CONCLUSION: Concurrent RCT with 5-FU/cisplatin has been associated with acceptable acute and long-term toxicity. Overall and cause-specific survival rates are encouraging. More than 80% of patients preserved their well-functioning bladder.	bladder